Formaldehyde → HCID 131735236, compound

Participants

Reaction Steps

A solution of 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate (1 g, 3.89 mmol) in THF (5 mL) was stirred at −78° C. and lithium bis(trimethylsilyl)amide (1M in toluene, 5.8 mL, 29 mmol) was added dropwise, then stirred for 1 h. Paraformaldehyde (0.7370 g, 7.773 mmol) was added and the mixture was stirred for 16 h, allowing the temperature to rise slowly to ambient. The reaction mixture was quenched using saturated aqueous ammonium chloride solution, then partitioned between EtOAc and brine. The aqueous layer was further extracted using EtOAc. The combined organic extracts were dried (MgSO4) and the solvent was removed under vacuum. The resulting material was dissolved and stirred for 1 h in TFA (10 mL), then rotary evaporated to dryness. The crude residue (theoretical 0.7 g, 3.891 mmol) was dissolved in ethanol (12 mL), then sodium carbonate (1.03 g, 9.72 mmol) and (2-chloropyrimidin-5-yl)boronic acid (0.68 g, 4.3 mmol) were added and the reaction mixture was stirred at 60° C. for 2 h. LC/MS showed completion of reaction. The mixture was cooled to ambient temperature and filtered through celite. The solvent was removed to give the crude title compound (1 g, 83%) as a cream solid, which was used without further purification. LCMS (pH 10) MH+ 310, RT 0.95 minutes.

Provenance & Evidence